A fixed-dose combination (FDC) of a benzodiazepine (Alprazolam) and a non-selective beta-adrenergic blocker (Propranolol). This combination is primarily used for the short-term management of anxiety disorders with prominent somatic symptoms, such as palpitations, tremors, and sweating. Alprazolam acts centrally to reduce psychic anxiety, while Propranolol peripherally blocks the physical manifestations of anxiety mediated by catecholamines. This combination is intended for use when anxiety presents with significant autonomic symptoms and is not a first-line therapy. Its use is strictly regulated in India due to the high potential for dependence and abuse associated with Alprazolam.
Adult: One tablet (Alprazolam 0.25mg + Propranolol 20mg) two to three times daily, as directed by the physician. The lowest effective dose for the shortest duration should be used. Maximum daily dose should not exceed 3 tablets (Alprazolam 0.75mg + Propranolol 60mg) without specialist consultation.
Note: Take orally with or without food. Food may slightly delay absorption but does not significantly affect overall bioavailability. Tablet can be split if scored. Do not crush or chew unless advised. Administer at regular intervals. Avoid taking at bedtime if daytime sedation is problematic. Do not stop abruptly; taper dose under medical supervision.
This combination provides a dual mechanism: central anxiolysis and peripheral blockade of autonomic symptoms. Alprazolam potentiates the effect of the inhibitory neurotransmitter GABA at the GABA-A receptor in the central nervous system, leading to sedation, reduced anxiety, and muscle relaxation. Propranolol competitively blocks beta-1 and beta-2 adrenergic receptors, preventing the action of catecholamines (epinephrine, norepinephrine) on the heart (reducing heart rate, force of contraction) and other tissues, thereby alleviating physical symptoms like tremor, palpitations, and sweating.
Pregnancy: Category D (US FDA). Both drugs cross the placenta. Alprazolam use in late pregnancy can cause neonatal flaccidity, respiratory depression, and withdrawal symptoms. Propranolol may cause intrauterine growth restriction, neonatal bradycardia, and hypoglycemia. Use only if potential benefit justifies the potential fetal risk. Avoid especially in the first trimester and near term.
Driving: Patients should NOT drive or operate heavy machinery, especially when starting treatment or after a dose increase, as the drug causes drowsiness, dizziness, and impaired judgment and reaction time.
| Other CNS Depressants (Alcohol, Opioids, Barbiturates, other Benzodiazepines) | Additive CNS depression, risk of profound sedation, respiratory depression, coma, death. | Major |
| Potent CYP3A4 Inhibitors (Ketoconazole, Itraconazole, Clarithromycin, Ritonavir) | Markedly increase Alprazolam plasma levels, leading to excessive sedation and prolonged effect. | Major |
| CYP3A4 Inducers (Rifampicin, Carbamazepine, Phenytoin, St. John's Wort) | Decrease Alprazolam plasma levels, reducing efficacy and potentially causing withdrawal. | Major |
| Other Antihypertensives, Diuretics, Nitrates | Additive hypotensive effect, risk of severe dizziness and fainting. | Moderate |
| Digoxin | Propranolol may increase digoxin levels and additive effects on AV node conduction, risk of bradycardia. | Moderate |
| Insulin, Oral Hypoglycemics | Propranolol may mask tachycardia from hypoglycemia and potentially impair glucose recovery; may also potentiate hypoglycemia. | Moderate |
| Theophylline, Salbutamol | Propranolol antagonizes bronchodilator effect, can precipitate bronchospasm in asthmatics. | Major (in asthmatics) |
| Clonidine | Abrupt withdrawal of either can lead to severe rebound hypertension. Withdraw Propranolol first if discontinuing both. | Major |
| NSAIDs (e.g., Ibuprofen, Naproxen) | May antagonize the antihypertensive effect of Propranolol. | Moderate |
| Fluoxetine, Paroxetine (CYP2D6 inhibitors) | May increase Propranolol levels. | Moderate |
Same composition (Alprazolam (0.25mg) + Propranolol (20mg)), different brands: